Multi-organ kinetic modeling for Na[F]F pre-clinical total-body PET studies.

BACKGROUND

Total-body positron emission tomography (PET), already well-established in the pre-clinical setting, makes it possible to study multi-parameters in biological systems as a whole, rather than focusing on single tissues analysis. Simultaneous kinetic analysis of multiple organs poses some daunting new challenges.

PURPOSE

To explore quantifying the pharmacokinetics of Na[F]F in multiple dissimilar murine organs simultaneously in vivo with total-body PET imaging using different compartmental models for each organ and a shared cardiovascular system.

METHODS

Six mice underwent a 60-min total-body PET scan following intravenous bolus injection of Na[F]F. Compartmental models were constructed for each organ (heart, lungs, liver, kidneys, and bone) using an image derived input function. Non-linear least squares fitting of a model that connects the five organs to a shared cardiovascular system was used to analyze both the first 3 min of data and the full hour. Analysis was repeated 5000 times using different initial parameter values for each duration, permitting analysis of correlations between parameters.

RESULTS

The models give a good qualitative account of the activity curves irrespective of the duration of the data; however, the quality of the fits to 3 min of data (average is 2.72) was generally better. Comparison of perfusion values to literature values was possible for the liver and lungs with the former (liver, 0.540 ± 0.177 mL/ml/min) being well-above expectations and the latter (lungs, 0.184 ± 0.413 mL/ml/min) in rough agreement. Correlations between microparameter values (especially affecting k) caused very noticeable problems for data modeling from both the kidneys and the femur.

CONCLUSION

The present study demonstrates an approach to performing kinetic modeling for multiple organs simultaneously with Na[F]F. The observed correlations between microparameter values remain a challenge. Nonetheless, many microparameters can be estimated reliably with a quantitative analysis of perfusion being possible for some organs.